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Biomedical subjects

D Heath

Publications and source records attributed to D Heath.

At least 19 recordsLinked to original sources
PubMed1992

The ultrastructure of pulmonary arteries and arterioles in emphysema.

The lungs from three cases of pulmonary emphysema obtained at heart-lung transplantation were examined by electron microscopy to determine the origin of intimal longitudinal muscle and the formation of muscular tubes in small pulmonary arteries and arterioles. The earliest change consisted of migration of mature smooth muscle cells from the media of small pulmonary arteries, through gaps in the internal elastic lamina, into the subendothelial space. Most of these cells then adopted a longitudinal orientation, maintained a muscular phenotype, and became enmeshed in a web of elastic fibres. A small minority, immediately subjacent to the endothelium, were orientated circularly and, in some vessels, were enclosed by rudimentary internal and external elastic laminae to form early muscular tubes. Pulmonary arterioles, which are normally devoid of a media, contained several layers of circularly orientated smooth muscle cells, some of which also formed muscular tubes. It is postulated that the limited migration of mature smooth muscle cells seen in states of chronic hypoxia is mediated by a different stimulus from that causing the florid invasion of the intima by immature smooth muscle, with subsequent transformation into myofibroblasts, which characterize plexogenic pulmonary arteriopathy.

Adult↗
PubMed1992

Mast cells in the human lung at high altitude.

Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were Mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.

Adult↗
PubMed1992

Nodules resembling arachnoid villi in pulmonary venules in plexogenic pulmonary arteriopathy.

We have found nodules histologically resembling arachnoid villi adjacent to pulmonary venules in a woman of 30 years with primary pulmonary hypertension. Such lesions have been reported previously in cases of mitral stenosis and pulmonary thromboembolism and we believe them to absorb excess water from the interstitial tissues of the alveolar walls, thus protecting the lung from the development of edema. In this way they seem to have a similar function to that of cerebral arachnoid villi and granulations which transport cerebrospinal fluid into the dural sinuses.

Adult↗
PubMed1992

The rat is a poor animal model for the study of human pulmonary hypertension.

The pulmonary circulation of the rat is widely used as an animal model for studies of human pulmonary hypertension. It is not difficult to understand its appeal. The species is a small laboratory animal which is readily accommodated in decompression chambers for studies for simulated high altitude. It is also very susceptible to the action of the metabolites of pyrrolizidine alkaloids which rapidly lead to severe pulmonary vascular disease in the absence of intrinsic heart and lung disease, thus suggesting its value as an animal model of primary pulmonary hypertension. However, these obvious advantages of the rat pulmonary circulation are outweighed by the fact that its pathological reactions to hypoxia and noxious dietary agents differ significantly from those found in human disease. This can lead to erroneous conclusions as to the nature of the remodelling of the human pulmonary vasculature in pulmonary hypertension.

Animals↗
PubMed1991

Influence of hypobaric hypoxia in infancy on the subsequent development of vasoconstrictive pulmonary vascular disease in the Wistar albino rat.

A group of Wistar albino rats was injected subcutaneously with monocrotaline to induce vasoconstrictive hypertensive pulmonary vascular disease characterized by medial hypertrophy of small pulmonary arteries, the appearance of muscular pulmonary arterial vessels of arteriolar dimensions (less than 20 microns) in diameter), and exudative changes in the lung parenchyma. The vascular abnormalities were quantified by measuring the percentage medial thickness of small pulmonary arteries, the number of muscular pulmonary arterial vessels below 20 microns in diameter per cm2 of lung section and by determining the smallest arterial vessels in each case showing muscularity. A second group of rats was born in a decompression chamber and kept in hypobaric hypoxia for a month of the neonatal period, developing hypoxic hypertensive pulmonary vascular disease as a consequence. The animals in this group were allowed to recover in room air for a period of 3 months and were then injected with the same dose of monocrotaline as that given to the first group. The rats previously exposed to hypoxia exhibited an exaggerated response to the alkaloid, showing in particular many more small muscular pulmonary arterial vessels which were of a smaller diameter than those found in the eupoxic rats treated with the alkaloid. The experiment demonstrates the perinatal hypoxia exaggerates the effects of agents inducing vasoconstrictive pulmonary hypertension with a shift of the segment of the pulmonary arterial tree involved to the periphery as in hypoxia. Reports of a similar phenomenon are noted as occurring in babies born at high altitude, spending their infancy there and subsequently developing primary pulmonary hypertension later in life.

Adult↗
PubMed1991

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz.

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600-3800 m, were significantly larger than those in age-matched controls from sea level (15.3 g vs 10.4 g; P less than 0.001) and appeared hyperplastic. The pituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P less than 0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

Adrenocorticotropic Hormone↗
PubMed1991

Pulmonary vascular remodelling in a high-altitude Aymara Indian.

A histological study of the pulmonary vasculature in a young male high-altitude Aymara Indian revealed four aspects of interest. There was muscularization of the terminal portion of the pulmonary arterial tree to involve pulmonary arterioles as small as 15 microns in diameter, thus forming a basis for the slightly increased pulmonary vascular resistance of native highlanders. Intimal longitudinal muscle was found in pulmonary arteries and arterioles and though to be due to chronic alveolar hypoxia. Inner muscular tubes similar to those found in chronic obstructive lung disease were present. Pulmonary veins and venules also showed intimal muscularization suggesting that alveolar hypoxia affects vascular smooth muscle cells per se irrespective of their situation. The nature of the remodelling in a pulmonary blood vessel depends on a combination of hypoxia and haemodynamics.

Adult↗
PubMed1991

Lung mast cells in plexogenic pulmonary arteriopathy.

The numbers of mast cells/mm2 of lung parenchyma were counted in four controls, 15 cases of primary plexogenic pulmonary arteriopathy (PPA), and 17 cases in which the arteriopathy was secondary to congenital heart disease, to determine if increased numbers occur in PPA and with what stage of disease they might be associated. Considerable accumulations of lung mast cells may occur in this disease, but these are not closely related to any particular histological stage in the development of the arteriopathy. It is postulated that while mast cells could conceivably exert a vasodilatory effect on constricted small pulmonary arteries, it seems more likely that they are part of the parenchymal changes that commonly develop in this disease.

Adolescent↗
PubMed1991

Pulmonary peptides, norepinephrine and endocrine cells in monocrotaline pulmonary hypertension.

The concentrations of norepinephrine and of the peptides bombesin, calcitonin gene-related peptide and neurotensin were measured in rats with monocrotaline pulmonary hypertension. The numbers of pulmonary endocrine cells showing positive immunoreactivity for calcitonin, calcitonin gene-related peptide, protein gene product 9.5 and bombesin were counted in a second group of rats with monocrotaline pulmonary hypertension. The concentration of norepinephrine in the lungs decreased significantly in the test rats but this could be attributed to dilution by an increased mass of tissue. The pulmonary concentration of all three peptides showed a decrease in the rats treated with monocrotaline but this was highly significant only in the case of bombesin. The pulmonary content of bombesin showed a substantial and significant decrease in the test rats. No neuroendocrine cells immunopositive for bombesin were identified in any of the control or test rats. There was no difference between the control and test rats with respect to the form or distribution of the cells immunoreactive for the other three The lack of pulmonary endocrine cells showing immunoreactivity for bombesin may be related to the absence of intimal proliferation in the pulmonary arteries in this species. This is in striking contrast to what occurs in plexogenic pulmonary arteriopathy in man and suggests that monocrotaline-induced pulmonary hypertension in rats is not a good animal model for this disease.

Animals↗
PubMed1990

Mechanism of glucocorticoid regulation of alkaline phosphatase gene expression in osteoblast-like cells.

In the rat osteosarcoma cell line ROS 17/2.8, glucocorticoids increase the activity of the plasma membrane enzyme, alkaline phosphatase. To determine the mechanisms responsible for this effect, we have studied the actions of dexamethasone on alkaline phosphatase activity, immunoreactive protein, and steady-state mRNA levels. Dexamethasone treatment increased both specific activity of alkaline phosphatase and the cell surface expression of immunoreactive protein in a dose-dependent manner, with a half-maximal increase at 2 nM. Steady-state alkaline phosphatase mRNA levels were also increased in a dose-dependent manner. The time course of dexamethasone induction occurred relatively slowly, with a lag period of 12 h before any discernable effect on alkaline phosphatase mRNA levels. The rise in alkaline phosphatase mRNA levels was attributable entirely to changes in gene transcription, with no effect on message stability. Treatment of ROS 17/2.8 cells with actinomycin D completely abolished the dexamethasone-induced rise in alkaline phosphatase mRNA levels. Measurement of alkaline phosphatase mRNA degradation, by incubation of cells with the transcriptional inhibitor 5,6-dichloro-ribofuranosylbenzimidazole, indicated an apparent half-life of 24 h in both untreated and dexamethasone-stimulated cells. The protein synthesis inhibitors cycloheximide and puromycin blocked the dexamethasone induction of alkaline phosphatase mRNA. These data suggest that the dexamethasone-induced rise in alkaline phosphatase gene transcription requires the synthesis of an unknown mediator protein.

Alkaline Phosphatase↗
PubMed1990

Monoclonal antibodies to ROS 17/2.8 cells recognize antigens, some of which are restricted to osteoblasts and chondrocytes.

We have raised a panel of 15 monoclonal antibodies (MAbs) recognizing cell surface antigens of the rat osteoblast-like cell line ROS 17/2.8. The MAbs were selected on the basis of preferential binding to ROS 17/2.8 cells compared to ROS 25/1 cells. Immunohistochemical studies of antigen localization on cryostat sections of rat calvaria, long bone, and soft tissues demonstrated that five of these MAbs, UBIM 1, 2, 3, 12, and 17, recognize antigens that are restricted to normal rat osteoblasts and chondrocytes. The antigens appear to be localized to the cell surface of the osteoblast, with no apparent staining of bone matrix in either undecalcified or decalcified sections. In vitro, these MAbs recognize cell surface antigens present on two additional cell lines, ROS 24/1 and Rat 2 cells, and on the adherent cell population cultured from rat long bone marrow. Of these MAbs, three (UBIM 1, 2, and 3) recognize high-molecular-weight antigens of Mr 200,000-225,000. This study has also identified cell surface antigens of ROS 17/2.8 cells that are not expressed by osteoblasts in vivo. MAbs UBIM 9 and 21 bind to marrow cells in long bone sections, to the 7-day-old nonadherent cell population from cultured marrow, and to lymphoid tissue in sections of spleen. Another four MAbs (UBIM 10, 11, 14, and 22) bind to a variety of cells and tissues both in vitro and in vivo. Studies of the interactions of this panel of MAbs with osteogenic tissues and cell lines may have an important impact on the understanding of osteoblast physiology.

Animals↗
PubMed1990

The ultrastructure of plexogenic pulmonary arteriopathy.

The lungs from 16 cases of plexogenic pulmonary arteriopathy obtained at heart-lung transplantation, half of which had primary pulmonary hypertension, were examined by electron microscopy. From these the probable pathogenesis of pulmonary arterial intimal fibrosis in plexogenic pulmonary arteriopathy was deduced. The earliest detectable change was migration of smooth muscle cells from the media, through the internal elastic lamina into the intima. These cells collected beneath the endothelium and lost many of their myofilaments to become myofibroblasts. They were associated with ground substance but scanty collagen fibrils. As the quantity of interstitial collagen increased, the myofibroblasts reverted to a muscular structure, became elongated, and assumed a regular, circumferential orientation. This later stage coincided with the development of plexiform lesions. At both early and later stages, the muscular pulmonary arteries were contracted but not markedly so, and muscular evaginations were not seen. On the other hand, the cellular intimal proliferations developed early and were occlusive. This suggests that occlusion of small pulmonary arterial vessels by myofibroblasts may be at least as important as vasoconstriction in the early elevation of the pulmonary vascular resistance in primary pulmonary hypertension.

Adolescent↗